We propose to continue our multidisciplinary multiyear research program, which will integrate substantial institutional expertise in infectious diseases, neurology, ophthalmology, gynecology, oncology, pharmacology, immunology, retrovirology, herpes viruses, and numerous clinical resources in both North and South Carolina, focusing on the evaluation of novel therapies for HIV-infected persons. Clinical investigators at UNC and six satellite units in Raleigh (Wake County Department of Health, Central Prison, and the Women's Prison), Greensboro, Charlotte, and Charleston, SC, will study new compounds active against HIV and associated infections, malignancies, and neurologic disorders in new patients and follow previously enrolled patients. We will continue our high rate of accrual among minorities, women, and IV drug users. The trials will be of all phases (I, Il, and Ill) and types. Patients will be followed for in vivo evidence of study drug effects on HIV, MAC (Mycobacterium avium intracellulare complex), CMV (cytomegalovirus), HSV (herpes simplex virus), and other opportunistic infections using our ACTG-certified retrovirology and herpes virus laboratory, as well as UNCH Laboratories. Pharmacokinetics will be monitored in our General Clinical Research Center. Concepts for new protocols will originate by our participation in ACTG committees (executive, neurology, primary infection, immunology) and by our established scientific advisory board. In particular, we have enclosed new concepts for three trials on cryptococcal meningitis (IL-12, M-CSF, gamma interferon), a phase I hydroxyurea trial, a phase Ill protease inhibitor, and a phase l trial of activated cytotoxic lymphocytes. Outreach to the community will be accomplished through our community advisory boards at each site and through our statewide newsletter. Finally, low protocol costs will be maintained by cost sharing with NIH grants (GCRC, Pediatric ACTU), as well as with UNC Hospitals, and the Department of Medicine.